Over half of US high school students express a low interest in science, technology, engineering and mathematics (STEM) careers-even among students with high proficiency. According to the National Science Foundation, the US faces a gathering storm due to a deficit of STEM professionals--including biomedical research (BR). Therefore, we propose the Early Preparation and Inspiration for Careers in the Biomedical Sciences (EPIC) Intervention, a partnership between a research university, four regional high schools, career planning experts, leaders in epidemiology education for grades 6-12, and community stakeholders. Specific Aims: 1) Determine whether interest, motivation and/or preparedness to pursue a BR career are greater among students who receive the Think Like an Epidemiologist Challenge (Epi Challenge) intervention compared with students who do not; 2) Determine whether adoption of career assessment and planning tools by high school career counselors influences motivation and/or preparedness to pursue a BR career. Design: Randomized intervention study with pre-/post testing. Methods: We will conduct a stratified random sample of 9th grade students in four high schools stratified by school, STEM interest/proficiency, with oversampling for economically disadvantaged and racial/ethnic minority status. In order to achieve balance in the intervention arms, each of the four strata will be randomized to receive or not receive a hypothesis-driven, mentor-guided project-based learning experience with follow-up through 12th grade. Major Hypothesis: Students who participate in the Epi Challenge in their freshman and sophomore years will be more likely to declare a STEM major by their senior year of high school. This intervention will provide basic training in epidemiologic methods, and will provide an authentic experience wherein student teams develop their own hypothesis, plan, conduct, analyze, interpret, and communicate results. Student teams will be mentored by second year Penn State graduate students. Other outcomes of interest include measures of increased inspiration about science (self-reported interest and self-efficacy), proficiency (science literacy, science inquiry skills, science and math grades and test scores), and persistence (self-reported career plan, job shadowing experience, elective course selection and dual enrollment). Expected Outcome: EPIC will provide an important longitudinal perspective on an early high school intervention related to later college choices among students at diverse high schools. Health Relevance: Addressing shortages in STEM careers in general and BR careers in particular will maintain and improve the knowledge and practice base for biomedical research, including health promotion and disease prevention.